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PubMed2006

Delayed occurrence of H-ras12V-induced hepatocellular carcinoma with long-term treatment with cinnamaldehydes.

Cinnamaldehyde from the bark of Cinnamomum cassia has been reported to have antitumor activity mediated by the inhibition of farnesyl transferase. We assessed in vivo the chemo-preventive effect of cinnamaldehydes on H-ras12V-induced hepatocellular carcinoma formation. A mouse model of hepatocellular carcinoma was established by using the transgene of mutated H-ras12V under the regulation of albumin enhancer/promoter. When treated with cinnamaldehyde for 10 weeks, hepatic tumor development was delayed with 2'-benzoyloxycinnamaldehyde (BCA) compared with control hepatocellular carcinoma formation. The effect of 2'-hydroxycinnamaldehyde (HCA) was comparable. The number of lesions and the size of each lesion were significantly reduced by BCA. Cell proliferation in the lesion was detected by incorporation of 5-bromo-2'-deoxyuridine (BrdU). BCA increased the number of splenocytes, concanavalin A-stimulated splenocyte proliferation and the infiltration of lymphocytes into liver. Data suggest that the delayed hepatic tumor development observed with BCA could be mediated by a long-term immunostimulating effect on T cells.

Acrolein↗
PubMed2006

Challenges in cryopreservation of clouded leopard (Neofelis nebulosa) spermatozoa.

The clouded leopard (Neofelis nebulosa) is an endangered species that is difficult to breed in captivity. Species management could benefit from the use of artificial insemination (AI) with frozen-thawed spermatozoa, but there have been no detailed studies of sperm cryosensitivity. The purposes of this study were to: (1) re-characterize seminal characteristics in the clouded leopard 20 years after the first descriptive studies Wildt et al., [Wildt DE, Howard JG, Hall LL, Bush M. Reproductive physiology of the clouded leopard. I. Electroejaculates contain high proportions of pleiomorphic spermatozoa throughout the year. Biol Reprod 1986; 34: 937-947]; and (2) conduct a comparative cryopreservation study on the feasibility of sperm from this species surviving a freeze-thawing stress. Ejaculates were collected from five adult males and subjected to standard analysis, followed by a two-step straw freezing protocol that evaluated the impact of thawing, dilution, centrifugation and in vitro culture (through 4 h) on sperm motility and acrosomal integrity. Additionally, we assessed the impact of both a traditional permeating cryoprotectant (glycerol at a final dilution of 4%) and an unconventional nonpermeating trisaccharide; raffinose (R) at a final dilution of 4% or 8%, with or without 4% glycerol on sperm cryosurvival. The clouded leopard produced an extremely poor quality ejaculate; although approximately 70% of fresh sperm were motile, >80% were malformed. Phase contrast microscopy revealed that 40% of all sperm had abnormal acrosomes, but Coomassie blue staining indicated that acrosomal abnormalities existed in almost 70% of spermatozoa. Upon freeze-thawing, sperm motility declined markedly (P < 0.05) by an average of 40%, regardless of diluent used. Interestingly, raffinose was as effective as glycerol in protecting both sperm motility and acrosomal integrity. Although no acrosomal damage was seen immediately after thawing, < 6% morphologically normal intact acrosomes were present by the last measured time point. In conclusion, the clouded leopard is a rare felid that (at least in North American zoos) is producing extraordinarily poor quality ejaculates. There are so many sperm with unexplained deranged acrosomes that it will be particularly challenging to use traditional AI with thawed sperm as an adjunct management tool.

Animals↗
PubMedDate not supplied

Antidepressants restore hypothalamic-pituitary-adrenal feedback function in aged, cognitively-impaired rats.

Aged, cognitively-impaired rats (and humans) show hypothalamic-pituitary-adrenal (HPA) hyperactivity that correlates with hippocampal damage. The resultant increase in plasma glucocorticoid exposure is thought to contribute to impaired hippocampal function and to potentiate hippocampal neuron death. In young, adult rats antidepressant drugs increase corticosteroid receptor expression in brain regions known to regulate the HPA axis, leading to increased negative-feedback control and decreased HPA activity. In the present study we examined basal levels of plasma adrenocorticotropin hormone (ACTH) and corticosterone in aged, cognitively-impaired (AI), aged, cognitively-unimpaired (AU) and young, adult (Yg) rats. Plasma ACTH and corticosterone levels were significantly elevated in the AI rats, but only in samples obtained during the diurnal peak. Five weeks of treatment with desipramine (15 mg/kg) significantly reduced evening levels of both ACTH and corticosterone in all groups, and eliminated the group differences. We then examined delayed, glucocorticoid negative feedback in these animals. Among vehicle-treated animals, a bolus injection of corticosterone (10 mg/kg), administered 3 hours prior to testing, completely inhibited the plasma ACTH response to restraint in AU and Yg, but not AI animals. In contrast, plasma ACTH responses to restraint were completely inhibited in AI rats following chronic treatment with desipramine. These findings indicate that the antidepressant, desipramine, decreases HPA activity and increases glucocorticoid negative-feedback sensitivity in AI rats, suggesting that antidepressant drugs may form a useful therapeutic approach to HPA dysfunction in elderly human populations.

Adrenocorticotropic Hormone↗
PubMed2002

A preliminary retrospective treatment and pharmacoeconomic analysis of asthma care provided by allergists, immunologists, and primary care physicians in a teaching hospital.

Allergy immunology specialists (AIs) differ from primary care physicians (PCP) in their treatment of asthma. A limited retrospective chart review of several visits over a 1-year period in 1997 evaluating the quality of asthma care by AIs vs. PCPs was conducted in an academic center. Data concerning quality, effectiveness and cost of asthma care was randomly collected from 15 AIs and 15 PCPs from charts at 3-month intervals over a 1-year period. Information obtained from data collection forms revealed that asthma patients evaluated by AIs had more visits and received a greater quantity of medication compared to those treated by PCPs. All 15 patients with persistent asthma followed by AIs were treated with inhaled corticosteroids at each visit in contrast to only 80% of those treated by PCPs. The total numbers of controller medications (i.e., inhaled corticosteroids, salmeterol, cromolyn, and theophylline) that were utilized, as recommended, by the National Asthma Expert Panel (NAEP) of the National Heart, Lung, and Blood Institute (NHLBI) guidelines were 70 by AIs vs. 24 by PCPs over three visits. Cromolyn was prescribed five times over three visits by AIs and not at all by PCPs. Recognition and treatment of coexisting allergic rhinitis was evident in only 13% of patients treated by PCPs as compared to 80% in those treated by AIS. (p < 0.0001). However, all patients treated by AIs were skin tested to explore the presence of allergic triggers, while no patients treated by PCPs were evaluated for IgE-mediated reactions. Treatment cost for allergic rhinitis was therefore higher, at $2039, for AIs as compared to $741 for PCPs. There were no peakflow values in charts obtained from PCPs. However, all charts from AIs had peakflow values, which improved during the course of therapy in 33% of patients. Total medication costs for asthma were higher for AIs @ $5,646.30 vs. $1,932.25 for PCPs. Total medication costs for allergic rhinitis plus asthma were higher for AIs @ $7615 vs. $2681 for PCPs. However, patients treated by AIs had more severe asthma and required more frequent visits. Ipratropium bromide was prescribed a total of four times over several visits by PCPs vs. only once by AIs. In comparing asthma care between AI specialists and PCPs, it was found that AI specialists treat more severe asthmatics, provide more frequent follow-up visits, utilize peak flow rates, prescribe more controller medications, and more often recognize and treat comorbid conditions such as allergic rhinitis that impact on asthma care. Thus, although treatment costs for AIs are higher, these costs are justified by a quality of care that is more consistent with national (NHLBI) guidelines.

Adult↗
PubMed2006

Hemostatic activation and outcome after recombinant tissue plasminogen activator therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: Early thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rtPA) improves clinical outcome in acute ischemic stroke (AIS), but impaired endogenous fibrinolysis, thrombin generation, and vascular injury may hamper the efficacy of thrombolysis. We investigated in an exploratory, post hoc analysis the relationship between hemostatic markers and clinical outcomes among patients included in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study. METHODS: Tissue plasminogen activator (tPA) antigen, thrombin-antithrombin complex (TAT), soluble thrombomodulin, and fibrinogen levels were measured in patients with AIS included in the NINDS rtPA Stroke Study from plasma samples collected at baseline, at 2 hours after treatment, and after 24 hours. RESULTS: TAT and tPA antigen levels peaked at 2 hours selectively in the rtPA treatment group, whereas fibrinogen levels dropped at 2 hours and remained low after 24 hours (P<0.0001 for interaction effects between time and treatment). At 24 hours, higher levels of tPA antigen were associated with a lower chance of favorable outcome (odds ratio [OR]=0.34; 95% CI, 0.14 to 0.82) selectively in the rtPA group, and higher levels of TAT (OR=1.72; 95% CI, 1.26 to 2.34) in the entire cohort and of thrombomodulin selectively in the rtPA group (OR=4.45; 95% CI, 1.26 to 15.67) were associated with higher 3-month mortality. CONCLUSIONS: Hemostatic activation after AIS appears to be independently associated with clinical outcome in patients treated with rtPA. However, because we have tested for multiple associations, some may have been identified by chance alone and require further confirmatory studies. On the basis of this exploratory analysis, there is a rationale to investigate the safety and efficacy of protocols in which rtPA is complemented by agents that are antithrombotic and enhance fibrinolysis.

Acute Disease↗
PubMed2003

[Association between AvaII exon 13 polymorphism at the LDL receptor gene different and serum lipid levels in normotensives and essential hypertensives in Shanghai].

OBJECTIVE: To investigate the AvaII polymorphism of low density lipoprotein receptor gene in both health and essential hypertension populations, and to evaluate the association of AvaII polymorphism with level of blood lipid. METHODS: Using polymerase chain reaction (PCR), AvaII polymorphism was studied in 109 health individuals and 319 patients with essential hypertension. RESULTS: There were three kinds of genotype: (+/+), (+/-), (-/-). The frequencies of the three genotypes were shown as follows: (+/+) 0.9%, (+/-) 27.5%, (-/-) 71.6% in health population and (+/+) 1.2%, (+/-) 33.9%, (-/-) 64.9% in essential hypertension population, respectively. The frequencies of the two alleles were shown as follows: (+) 14.7%, (-) 85.3% in health population, (+) 18.2%, (-) 81.8% in essential hypertension population and (+) 17.3%, (-) 82.7% in the community, respectively. In male essential hypertension cases, the genotypes were associated with serum TC and LDL-C level in the following order: (-/-) < (+/-) (P < 0.05). In women and healthy population, there was a similar trend but not statistically significant (P > 0.05). CONCLUSIONS: A significant association was found between the common variation of LDL-R gene and serum TC and LDL-C levels. (+) Allele was associated with elevated level of serum TC and LDL-C, but (-) allele was associated with a low level of serum TC and LDL-C. The frequencies of (-) allele in both group were related to serum low level TC while LDL-C was much higher than that reported in the western countries. These data indicated that genetic factors which resistant to hypercholesterolemia in Chinese people were different from those findings in West while might be one of the reasons to explain why that serum TC level in Chinese was lower than people in the western countries.

Adult↗
PubMed2004

[Clinical observation on effect of xuesaitong injection as auxiliary treatment of severe craniocerebral injury].

OBJECTIVE: To evaluate the effect of Xuesaitong injection (XSTI, a preparation of Panax Notoginseng) as auxilliary treatment of severe craniocerebral injury. METHODS: Eighty-seven patients with severe craniocerebral injury were selected and randomly divided into the treated group (n = 44) and the control group (n = 43), they were treated with conventional treatment, and XSTI was given additionally to the treated group. Intracranial pressure (ICP) and Glasgow coma score (GCS) of all patients were measured after 1 or 2-week treatment, and Glasgow outcome scale (GOS) of them was determined 3 months later. Then the therapeutic effect in the two groups were compared. RESULTS: After treatment, the ICP was lower, GCS higher and GOS better in the treated group than those in the control group significantly, all showing statistical significance (P < 0.05). CONCLUSION: XSTI has marked clinical therapeutic effect in treating patients with severe craniocerebral injury.

Adult↗
PubMed2005

[Preventive and therapeutic effects of recombinant IFN-alpha2b nasal spray on SARS-CoV infection in Macaca mulata].

OBJECTIVE: To study the preventive and therapeutic effects of recombinant IFN-alpha2b for nasal spray on SARS-CoV infection in Macaca mulata (rhesus monkey). METHODS: Ten rhesus monkeys were divided into two groups, 5 in interferon group, and 5 in control group. Before and after SARS-CoV attack, the virus was detected in samples such as pharyngeal swab in all the two groups by Real-time PCR (RT-PCR) and virus isolation was performed. RESULTS: After virus attack, the level of SARS-CoV-specific IgG and neutralizing antibody were induced by SARS-CoV in the interferon group was weaker than in control group. Hematology items showed no apparent changes after virus attack in treated group. Through pathological examination, the morphology of the lung tissues of two Macaques in the treated group was normal, while the other three displayed the interstitial pneumonia with the thickened septum and infiltration with mononuclear cells. Among which, one monkey showed part of thickened septum fused with each other. These lesions in the interferon treated animals were similar to those seen in the animals in control group, but with smaller scope of pathological changes. No significant abnormity was detected in other organs. CONCLUSION: Recombinant IFN-alpha2b could effectively interdict or weaken SARS-CoV injury in monkeys.

Animals↗
PubMed1995

Interrelationships between the renin angiotensin system and uteroplacental blood flow--a recent perspective.

In pregnancy, the maternal circulating renin-angiotensin system (RAS) and uteroplacental tissue RAS has been thought to support maternal placental flow by raising maternal arterial pressure or changing placental vascular resistance. Also, the placenta or uterus may alter maternal circulating RAS. Recent studies in the authors' laboratory using chronically catheterized rabbits are compared with previous studies on interactions between the RAS and uteroplacental flow. When uterine driving pressure was reduced either mechanically or after converting enzyme inhibition, maternal placental flow decreased in proportion to change in driving pressure; myoendometrial flow did not change. Angiotensin II (AII) infusion to increase pressure by 21 +/- 2 mm Hg decreased placental but not myoendometrial flow. Thus, there is no evidence that maternal placental flow is autoregulated or supported by a specific renin-angiotensin mechanism. Normally, there is no net uterine release or uptake of active plasma renin activity, AI, or AII, but there is a small net release of trypsin-activated plasma renin activity (tPRA), presumably prorenin. Distal aortic occluder inflation produced upper-body hypertension, and uterine release of tPRA increased. There was a significant uterine arteriovenous concentration difference for AII during AII infusion. These methods are adaptable for studying interactions between uteroplacental flow and other vasoactive agents.

Angiotensin II↗
PubMed2001

Paraoxonase genotype modifies the effect of pravastatin on high-density lipoprotein cholesterol.

Paraoxonase (PON) is an enzyme carried by high-density lipoprotein cholesterol (HDL-C). Two gene polymorphisms leading to amino acid substitutions of methionine for leucine at position 55 (M/L55) and arginine for glutamine at position 192 (R/Q192) modulate the activity of the enzyme and possibly also lipid and apolipoprotein concentrations. Our purpose was to examine the effect of the PON genotype on HDL-C and apolipoprotein AI (apo AI) responses to pravastatin treatment. Fifty-one mildly hypercholesterolemic male subjects (mean age 35 +/- 4 years) were enrolled by this prospective, randomized, double-blind study. Lipid concentrations were measured at baseline and after 6 months of pravastatin (n = 25) or placebo (n = 26) therapy. Low active (MM, ML or QQ) and high active (LL or RQ, RR) PON genotype groups were related to lipid and apolipoprotein concentration changes. Pravastatin increased the apo AI concentration 12% (P = 0.017, RANOVA) and tended to increase the HDL-C concentration (P = 0.095, RANOVA) in R allele carriers but not in QQ homozygotes. Significant predictors of the change in apo AI concentration during pravastatin treatment were R/Q192 genotype (P = 0.002), apo AI concentration at baseline (P = 0.002) and M/L55 genotype (P = 0.042). Correspondingly, R/Q192 (P = 0.009) and M/L55 (P = 0.050) genotypes were the statistically significant determinants of HDL-C concentration change. The PON genotype thus modifies the effect of pravastatin on serum HDL-C and apo AI concentrations. This could partly explain the contradictory results obtained from previous studies on the effects of statins on the serum HDL-C concentration.

Adult↗
PubMed2003

[Effects of quercetin on the proliferation and apoptosis in transplantation tumor of breast cancer in nude mice].

OBJECTIVE: To investigate the effects of quercetin on tumour growth, cell proliferation and apoptosis in transplantation tumor of breast cancer cell line MCF-7 in nude mice. METHODS: MCF-7 cells were inoculated into the mammary fatty pad of nude mice to establish breast cancer model, then twenty-four BALB/c nude mice with xenograft tumor were randomized into four groups: Control group, Quercetin group, 5-Fu group and Quercetin + 5-Fu group. After 15 days treatment, samples of tumor were collected. The sections of tumor were observed under light microscope and electron microscope. Cell apoptosis in situ was examined by a Tunel assay, and the expressions of ki67 antigen and B-cell lymphoma/leukemia-2 (Bcl-2) were detected by immunohistochemistry. RESULTS: 1. The tumor weight of Control group was significantly higher than those of Quercetin group, 5-Fu group and Quercetin + 5-Fu group (P < 0.05). 2. Immunohistochemical staining of ki67 showed that the ki67 label index (ki67-LI) displayed significant difference between Control group and Quercetin group, 5-Fu group, Quercetin + 5-Fu group, and so did the staining of Bcl-2. 3. Detection of apoptosis in situ showed that apoptosis index (AI) was significantly higher in Quercetin group, 5-Fu group and Quercetin + 5-Fu group than in control group (P < 0.01), and higher AI was observed in Quercetin + 5-Fu group as compared with the AI in Quercetin group and 5-Fu group (P < 0.05). CONCLUSION: Quercetin can inhibit the growth of transplantation tumor of breast cancer cell line MCF-7 in nude mice.

Animals↗
PubMed2026

Canalesolide A, a Structurally Unique Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania sp. with Potent Antitrypanosomal Activity.

The discovery of structurally novel natural products remains central to expanding biologically relevant chemical space, particularly within underexplored marine metabolite classes. Herein, we report the discovery and complete structural elucidation of canalesolide A, a new polyhydroxylated macrolide isolated from the marine cyanobacterium Okeania sp. The compound was identified through an integrated workflow combining phenotypic screening against Trypanosoma brucei and LC-MS/MS-based molecular networking, enabling rapid prioritization of bioactive fractions and dereplication of known metabolite families. Spectroscopic analysis revealed that canalesolide A belongs to the bastimolide-related class of macrolides but exhibits a distinct structural architecture. Its structure was established by integrating ultrahigh-resolution NMR spectroscopy, empirical configurational analysis of polyol systems, targeted model compound synthesis, and controlled chemical degradation and derivatization. This combined strategy resolved stereochemical motifs that were inaccessible by direct analysis of the intact macrolide alone, providing a transferable approach for assigning densely oxygenated marine macrolides. Genome mining identified the putative biosynthetic gene cluster and proposed biosynthetic pathway for a bastimolide-related macrolide. Canalesolide A displays potent, low nanomolar antitrypanosomal activity against human-infective subspecies of T. brucei with rapid elimination of parasites within 1 h at 1 &#x3bc;M. Although moderate mammalian cytotoxicity was observed, preliminary in vivo efficacy/toxicity studies in infected mice suggest a narrow therapeutic window highlighting the need for improved selectivity. This study expands the structural and biosynthetic diversity of polyhydroxylated macrolides and establishes a generalizable framework for resolving stereochemically complex natural products.

Macrolides↗
PubMed2004

New isoprenylated flavones, artochamins A--E, and cytotoxic principles from Artocarpus chama.

Five new isoprenylated flavones, artochamins A-E (1-5), together with eight known flavones (6-13), were isolated from the roots of Artocarpus chama. All structures were elucidated by spectroscopic methods. Artonin E (12) showed strong cytotoxicity against 1A9 (ovarian), significant activity against MCF-7 (breast adenocarcinoma), and moderate activity against HCT-8 (ileocecal) and MDA-MB-231 (breast adenocarcinoma) tumor cell lines. Artochamin C (3) was more potent against MCF-7, 1A9, HCT-8, and SK-MEL-2 (melanoma) than A549 (lung carcinoma), KB (epidermoid carcinoma of the nasopharynx), and its drug-resistant (KB-VIN) variant. Artocarpin (6) displayed weak but relatively broad inhibitory effects compared with 3 and 12.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Posttreatment 13C-urea breath test is predictive of antimicrobial resistance to H. pylori after failed therapy.

OBJECTIVE: We tested whether a 13C-urea breath test can predict antimicrobial resistance of Helicobacter pylori (H. pylori). METHODS: Seventy patients who had failed triple eradication therapy and 108 untreated H. pylori-infected patients were given a 13C-urea breath test, endoscopy for culture of H. pylori, and assessment of clarithromycin resistance. The patients who had failed triple therapy then received 1 week of quadruple therapy to eradicate residual H. pylori. RESULTS: The posttreatment value of the 13C-urea breath test expressed as excessive delta13CO2 per ml (ECR) was higher in patients with residual H. pylori with clarithromycin resistance than in those without (23.8 vs 10.6; P<.0001). With a cutoff of ECR >or< or =15, the 13C-urea breath test was 88.6% sensitive and 88.9% specific in predicting clarithromycin resistance of residual H. pylori. The H. pylori eradication rate of the rescue regimen was higher for patients with a posttreatment ECR of the 13C-urea breath test < or =15 than for those with a value >15 (93.8% vs 73.3%; P<.05). In contrast, in treatment-naive H. pylori-infected patients, the pretreatment value of the 13C-urea breath test did not differ between patients infected with clarithromycin-resistant or-sensitive isolates (P>.05). CONCLUSION: The posttreatment value of the 13C-urea breath test is predictive of clarithromycin resistance in residual H. pylori after failed triple therapy and predicts efficacy of the rescue regimen. The value of the noninvasive test is promising for primary care physicians who need to select a rescue regimen without invasive H. pylori culture.

Adult↗
PubMed2005

Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic purpura.

AIM: To determine whether mycophenolate mofetil (MMF) has beneficial effects on refractory idiopathic thrombocytopenic purpura (ITP) and the corresponding cellular mechanism. METHODS: Twenty refractory ITP patients resistant to corticosteroid and/or splenectomy and chemical therapy were given MMF 1.5-2.0 g/d orally for a 2 to 4-month period. Serum immunoglobulin was detected by rate nephelometry. Platelet-associated antibodies (PAIgG) were assayed by enzyme-linked immunosorbant assay. The immunophenotypic analysis was performed on a flow cytometer and cell apoptosis was detected with transferase mediated dUTP biotin nick end labeling (TUNEL) method. RESULTS: Sixteen of the 20 (80%) patients had responses to MMF treatment; 9 (45%) achieved a complete response, 4 (20%) achieved a partial response, and 3 (15%) achieved a minor response. The therapeutic effects were found to be better in male patients than female patients. The number of CD3+ peripheral blood cells (PBCs) and CD4+ PBCs increased and the number of CD8+ PBCs decreased. The plasma level of IgG, IgM, IgA and platelet associated IgG (PAIgG) decreased in 86% of the patients. TUNEL assay showed that mycophenolate acid (MPA) 0.1 mmol/L induced apoptosis of peripheral blood mononuclear cells isolated from refractory ITP patients. The apoptosis rate was increased in male patients after treatment with MPA, but was unchanged in female patients. CONCLUSION: Therapy for a period of 8 to 16 weeks with median-dose of MMF was valuable for the treatment of refractory ITP.

Adolescent↗
PubMed2004

Serum hepatic enzyme manifestations in patients with severe acute respiratory syndrome: retrospective analysis.

AIM: To evaluate the hepatic function in patients with severe acute respiratory syndrome (SARS) and possible causes of hepatic disorder in these patients. METHODS: One hundred and eighty-two patients with SARS were employed in a retrospective study that investigated hepatic dysfunction. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) were analyzed in these patients. Patients with different hospital treatments were further investigated. RESULTS: Of the 182 patients, 128(70.3%) had abnormal ALT activity, 57(31.3%) had abnormal AST activity and 87(47.8%) had abnormal LDH activity. The peak of elevated hepatic enzyme activities occurred between the sixth day and the tenth day after the first day of reported fever. Of the 182 patients, 160(87.9%) had been treated with antibiotics, 137(75.2%) with Ribavirin, and 115(63.2%) with methylpredisolone. There was no statistically significant correlation between the duration of Ribavirin treatment and hepatic dysfunction. CONCLUSION: Abnormal liver functions were common in patients with SARS and could be associated with virus replication in the liver.

Adolescent↗
PubMed2003

Heat shock protein 90 is responsible for hyperdynamic circulation in portal hypertensive rats.

AIM: To examine the participation of HSP90 in portal hypertensive rat mesentery in vitro. METHODS: Immunohistochemistry and Western-blot were used to examine the expression of HSP90 in mesenteric vasculature. HSP90 mRNA was detected by RT-PCR, and the role of HSP90 in hyperdynamic circulation was examined by in vitro mesenteric perfusion studies. RESULTS: HSP90 was overexpressed in endothelium of mesentery vasculature in animals with experimental portal hypertension induced by partial portal vein ligation (PVL) compared with normal animals. Geldanamycin (GA), a special inhibitor of HSP90 signaling, attenuated ACh-dependent vasodilation but did not affect vasodilation in response to sodium nitroprusside in normal rats. In PVL animals, the perfused mesentery was hyporesponsive to vasoconstrictor methoxamine. GA significantly potentiated methoxamine-induced vasoconstrictor after PVL. CONCLUSION: HSP90 plays a key role in NO-dependent hyperdynamic circulation in portal hypertension and provides a novel method for future treatment of portal hypertension.

Acetylcholine↗